View source for 5-HT2C receptor


{{Wrongtitle|title=5-HT<sub>2C</sub> receptor}}
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{{GNF_Protein_box
 | image =  
 | image_source =  
 | PDB = 
 | Name = 5-hydroxytryptamine (serotonin) receptor 2C
 | HGNCid = 5295
 | Symbol = HTR2C
 | AltSymbols =; 5-HT2C; HTR1C
 | OMIM = 312861
 | ECnumber =  
 | Homologene = 20242
 | MGIid = 96281
 | GeneAtlas_image1 = PBB_GE_HTR2C_211479_s_at_tn.png
 | GeneAtlas_image2 = PBB_GE_HTR2C_207307_at_tn.png
 | Function = {{GNF_GO|id=GO:0001584 |text = rhodopsin-like receptor activity}} {{GNF_GO|id=GO:0004872 |text = receptor activity}} {{GNF_GO|id=GO:0004993 |text = serotonin receptor activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} 
 | Component = {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}} {{GNF_GO|id=GO:0016020 |text = membrane}} 
 | Process = {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007210 |text = serotonin receptor signaling pathway}} {{GNF_GO|id=GO:0007268 |text = synaptic transmission}} {{GNF_GO|id=GO:0007631 |text = feeding behavior}} 
 | Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 3358
    | Hs_Ensembl = ENSG00000147246
    | Hs_RefseqProtein = NP_000859
    | Hs_RefseqmRNA = NM_000868
    | Hs_GenLoc_db =  
    | Hs_GenLoc_chr = X
    | Hs_GenLoc_start = 113724807
    | Hs_GenLoc_end = 114050880
    | Hs_Uniprot = P28335
    | Mm_EntrezGene = 15560
    | Mm_Ensembl = ENSMUSG00000041380
    | Mm_RefseqmRNA = XM_978183
    | Mm_RefseqProtein = XP_983277
    | Mm_GenLoc_db =  
    | Mm_GenLoc_chr = X
    | Mm_GenLoc_start = 142208881
    | Mm_GenLoc_end = 142443644
    | Mm_Uniprot = Q8BUB1
  }}
}}
{{CMG}}   
==Overview==
'''5-hydroxytryptamine (serotonin) receptor 2C''', also known as '''HTR2C''', is a [[5-HT2 receptor|5-HT<sub>2</sub> receptor]], but also denotes the human [[gene]] encoding it.
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==Function==
*CNS: anxiety, [[choroid plexus]]: [[cerebrospinal fluid]] (CSF) secretion

==Ligands==
Numerous (ex-)prescription, illicit and research drugs contain a 5-HT<sub>2C</sub> component in their binding profile, including [[fluoxetine]], [[mianserin]]<!--inverse agonist-->, [[clozapine]], [[agomelatine]], dextro-[[norfenfluramine]]<!--full agonist-->, [[psilocin]], [[2,5-Dimethoxy-4-iodoamphetamine|DOI]]<!--partial agonist-->, α-methyl-serotonin, MK-212, [[1-(3-Chlorophenyl)piperazine|''m''-CPP]]<!--partial agonist-->, FG-7142,<ref name="pmid17138863">{{cite journal | author = Hackler EA, Turner GH, Gresch PJ, Sengupta S, Deutch AY, Avison MJ, Gore JC, Sanders-Bush E | title = 5-Hydroxytryptamine2C receptor contribution to m-chlorophenylpiperazine and N-methyl-beta-carboline-3-carboxamide-induced anxiety-like behavior and limbic brain activation | journal = J. Pharmacol. Exp. Ther. | volume = 320 | issue = 3 | pages = 1023-9 | year = 2007 | pmid = 17138863 | doi = 10.1124/jpet.106.113357 | issn = }}</ref> Ro60-0175<!--agonist-->,<ref name="pmid11399662">{{cite journal | author = Higgins GA, Ouagazzal AM, Grottick AJ | title = Influence of the 5-HT(2C) receptor antagonist SB242,084 on behaviour produced by the 5-HT<sub>2</sub> agonist Ro60-0175 and the indirect 5-HT agonist dexfenfluramine | journal = Br. J. Pharmacol. | volume = 133 | issue = 4 | pages = 459-66 | year = 2001 | pmid = 11399662 | doi = 10.1038/sj.bjp.0704082 | issn = }}</ref> [[mesulergine]], [[metergoline]], [[ritanserin]], [[methiothepin]], 5-methoxy[[gramine]]<!--silent antagonist-->, and many more.<ref name="pmid17017967">{{cite journal | author = Lacivita E, Leopoldo M | title = Selective agents for serotonin 2C (5-HT<sub>2C</sub>) receptor | journal = Curr Top Med Chem | volume = 6 | issue = 18 | pages = 1927-70 | year = 2006 | pmid = 17017967 | doi = 10.2174/156802606778522168 | issn = }}</ref> Some compounds with a more pronounced selectivity for the 5-HT<sub>2C</sub> receptor subtype are listed below. Note, that in the following context the term "functional selectivity" does not refer to differentiation of transductional pathways.

=== Agonists ===
*YM348: potent, [[full agonist]], high [[Dissociation constant#Protein-Ligand binding|affinity]], high functional selectivity, orally active<ref name="pmid14709324">{{cite journal | author = Kimura Y, Hatanaka K, Naitou Y, Maeno K, Shimada I, Koakutsu A, Wanibuchi F, Yamaguchi T | title = Pharmacological profile of YM348, a novel, potent and orally active 5-HT<sub>2C</sub> receptor agonist | journal = Eur. J. Pharmacol. | volume = 483 | issue = 1 | pages = 37-43 | year = 2004 | pmid = 14709324 | doi = 10.1016/j.ejphar.2003.10.004 | issn = }}</ref><ref name="pmid18035544">{{cite journal | author = Shimada I, Maeno K, Kazuta K, Kubota H, Kimizuka T, Kimura Y, Hatanaka K, Naitou Y, Wanibuchi F, Sakamoto S, Tsukamoto S | title = Synthesis and structure-activity relationships of a series of substituted 2-(1H-furo[2,3-g]indazol-1-yl)ethylamine derivatives as 5-HT<sub>2C</sub> receptor agonists | journal = Bioorg. Med. Chem. | volume = 16 | issue = 4 | pages = 1966-82 | year = 2008 | pmid = 18035544 | doi = 10.1016/j.bmc.2007.10.100 | issn = }}</ref>

*(5a''R'',9''R'')-2-[(cyclopropylmethoxy)methyl]-5,5a,6,7,8,9-hexahydro-9-methyl-pyrido[3′,2′:4,5]pyrrolo[1,2-a]pyrazine: potent, full agonist with an outstanding selectivity profile<ref name="pmid16361098">{{cite journal | author = Richter HG, Adams DR, Benardeau A, Bickerdike MJ, Bentley JM, Blench TJ, Cliffe IA, Dourish C, Hebeisen P, Kennett GA, Knight AR, Malcolm CS, Mattei P, Misra A, Mizrahi J, Monck NJ, Plancher JM, Roever S, Roffey JR, Taylor S, Vickers SP | title = Synthesis and biological evaluation of novel hexahydro-pyrido[3',2':4,5]pyrrolo[1,2-a]pyrazines as potent and selective 5-HT<sub>2C</sub> receptor agonists | journal = Bioorg. Med. Chem. Lett. | volume = 16 | issue = 5 | pages = 1207-11 | year = 2006 | pmid = 16361098 | doi = 10.1016/j.bmcl.2005.11.083 | issn = }}</ref>

*(''R'')-9-ethyl-1,3,4,10b-tetrahydro-7-trifluoromethylpyrazino[2,1-a]isoindol-6(2''H'')-one: agonist, >300-fold functional selectivity over 5-HT<sub>2B</sub> and >70-fold over 5-HT<sub>2A</sub><ref name="pmid17315987">{{cite journal | author = Wacker DA, Varnes JG, Malmstrom SE, Cao X, Hung CP, Ung T, Wu G, Zhang G, Zuvich E, Thomas MA, Keim WJ, Cullen MJ, Rohrbach KW, Qu Q, Narayanan R, Rossi K, Janovitz E, Lehman-McKeeman L, Malley MF, Devenny J, Pelleymounter MA, Miller KJ, Robl JA | title = Discovery of (R)-9-ethyl-1,3,4,10b-tetrahydro-7-trifluoromethylpyrazino[2,1-a]isoindol- 6(2H)-one, a selective, orally active agonist of the 5-HT<sub>2C</sub> receptor | journal = J. Med. Chem. | volume = 50 | issue = 6 | pages = 1365-79 | year = 2007 | pmid = 17315987 | doi = 10.1021/jm0612968 | issn = }}</ref>

*[[Lorcaserin]]: full agonist, fair selectivity profile<ref name="pmid18252809">{{cite journal | author = Thomsen WJ, Grottick AJ, Menzaghi F, Reyes-Saldana H, Espitia S, Yuskin D, Whelan K, Martin M, Morgan M, Chen W, Al-Shama H, Smith B, Chalmers D, Behan D | title = Lorcaserin, A Novel Selective Human 5-HT<sub>2C</sub> Agonist: In Vitro and In Vivo Pharmacological Characterization | journal = J. Pharmacol. Exp. Ther. | volume = | issue = | pages = | year = 2008 | pmid = 18252809 | doi = 10.1124/jpet.107.133348 | issn = }}</ref><ref name="pmid15713408">{{cite journal | author = Smith BM, Smith JM, Tsai JH, Schultz JA, Gilson CA, Estrada SA, Chen RR, Park DM, Prieto EB, Gallardo CS, Sengupta D, Thomsen WJ, Saldana HR, Whelan KT, Menzaghi F, Webb RR, Beeley NR | title = Discovery and SAR of new benzazepines as potent and selective 5-HT<sub>2C</sub> receptor agonists for the treatment of obesity | journal = Bioorg. Med. Chem. Lett. | volume = 15 | issue = 5 | pages = 1467-70 | year = 2005 | pmid = 15713408 | doi = 10.1016/j.bmcl.2004.12.080 | issn = }}</ref><ref name="pmid18039773">{{cite journal | author = Lam DD, Przydzial MJ, Ridley SH, Yeo GS, Rochford JJ, O'Rahilly S, Heisler LK | title = Serotonin 5-HT2C Receptor Agonist Promotes Hypophagia via Downstream Activation of Melanocortin 4 Receptors | journal = Endocrinology | volume = 149 | issue = 3 | pages = 1323-8 | year = 2008 | pmid = 18039773 | doi = 10.1210/en.2007-1321 | issn = }}</ref>

=== Antagonists ===
*FR260010: [[silent antagonist]], high affinity, selective over 5-HT<sub>2A</sub> and many other receptors; orally active.<ref name="pmid17074317">{{cite journal | author = Harada K, Aota M, Inoue T, Matsuda R, Mihara T, Yamaji T, Ishibashi K, Matsuoka N | title = Anxiolytic activity of a novel potent serotonin 5-HT<sub>2C</sub> receptor antagonist FR260010: a comparison with diazepam and buspirone | journal = Eur. J. Pharmacol. | volume = 553 | issue = 1-3 | pages = 171-84 | year = 2006 | pmid = 17074317 | doi = 10.1016/j.ejphar.2006.09.042 | issn = }}</ref>

*RS-102221: silent antagonist, 100-fold selectivity compared to the 5-HT<sub>2A</sub> and -HT<sub>2B</sub> receptor subtypes<ref name="pmid9225287">{{cite journal | author = Bonhaus DW, Weinhardt KK, Taylor M, DeSouza A, McNeeley PM, Szczepanski K, Fontana DJ, Trinh J, Rocha CL, Dawson MW, Flippin LA, Eglen RM | title = RS-102221: a novel high affinity and selective, 5-HT<sub>2C</sub> receptor antagonist | journal = Neuropharmacology | volume = 36 | issue = 4-5 | pages = 621-9 | year = 1997 | pmid = 9225287 | doi = 10.1016/S0028-3908(97)00049-X | issn = }}</ref>

===Mixed response===
A more extensive examination on [[signal transduction]] was carried out for
*SB-243213: high affinity, >100-fold selectivity over a wide range of neurotransmitter receptors, enzymes and [[ion channel]]s; long duration of action in vivo (>8 h); [[anxiolytic]]-like effects.<ref name="pmid11489455">{{cite journal | author = Wood MD, Reavill C, Trail B, Wilson A, Stean T, Kennett GA, Lightowler S, Blackburn TP, Thomas D, Gager TL, Riley G, Holland V, Bromidge SM, Forbes IT, Middlemiss DN | title = SB-243213; a selective 5-HT<sub>2C</sub> receptor inverse agonist with improved anxiolytic profile: lack of tolerance and withdrawal anxiety | journal = Neuropharmacology | volume = 41 | issue = 2 | pages = 186-99 | year = 2001 | pmid = 11489455 | doi = 10.1016/S0028-3908(01)00054-5 | issn = }}</ref> ''[[Inverse agonist]]'' for the [[phospholipase A2|PLA2]] response, for [[GTPgammaS]] binding, for reduction of constitutive desensitization, and for enhancement of dopamine release in the rat [[nucleus accumbens]]. ''Silent antagonist'' for the [[phospholipase C|PLC]] cascade.<ref name="pmid16807362">{{cite journal | author = Berg KA, Navailles S, Sanchez TA, Silva YM, Wood MD, Spampinato U, Clarke WP | title = Differential effects of 5-methyl-1-{[2-[(2-methyl-3-pyridyl)oxyl]-5-pyridyl]carbamoyl}-6-trifluoromethylindone (SB 243213) on 5-hydroxytryptamine (2C) receptor-mediated responses | journal = J. Pharmacol. Exp. Ther. | volume = 319 | issue = 1 | pages = 260-8 | year = 2006 | pmid = 16807362 | doi = 10.1124/jpet.106.104448 | issn = }}</ref> (See also [[functional selectivity]]).

==Receptor regulation==
Agonists promote 5-HT<sub>2C</sub> receptor [[internalization (cell biology)|internalization]] leading to [[tachyphylaxis]].<ref name="pmid15113845">{{cite journal | author = Schlag BD, Lou Z, Fennell M, Dunlop J | title = Ligand dependency of 5-hydroxytryptamine 2C receptor internalization | journal = J. Pharmacol. Exp. Ther. | volume = 310 | issue = 3 | pages = 865-70 | year = 2004 | pmid = 15113845 | doi = 10.1124/jpet.104.067306 | issn = }}</ref>

==See also==
* [[5-HT receptor]]

==References==
{{Reflist|2}}

==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading 
| citations = 
*{{cite journal  | author=Niswender CM, Sanders-Bush E, Emeson RB |title=Identification and characterization of RNA editing events within the 5-HT2C receptor. |journal=Ann. N. Y. Acad. Sci. |volume=861 |issue=  |pages= 38-48 |year= 1999 |pmid= 9928237 |doi=  }}
*{{cite journal  | author=Hoyer D, Hannon JP, Martin GR |title=Molecular, pharmacological and functional diversity of 5-HT receptors. |journal=Pharmacol. Biochem. Behav. |volume=71 |issue= 4 |pages= 533-54 |year= 2002 |pmid= 11888546 |doi=  }}
*{{cite journal  | author=Raymond JR, Mukhin YV, Gelasco A, ''et al.'' |title=Multiplicity of mechanisms of serotonin receptor signal transduction. |journal=Pharmacol. Ther. |volume=92 |issue= 2-3 |pages= 179-212 |year= 2002 |pmid= 11916537 |doi=  }}
*{{cite journal  | author=Van Oekelen D, Luyten WH, Leysen JE |title=5-HT2A and 5-HT2C receptors and their atypical regulation properties. |journal=Life Sci. |volume=72 |issue= 22 |pages= 2429-49 |year= 2003 |pmid= 12650852 |doi=  }}
*{{cite journal  | author=Reynolds GP, Templeman LA, Zhang ZJ |title=The role of 5-HT2C receptor polymorphisms in the pharmacogenetics of antipsychotic drug treatment. |journal=Prog. Neuropsychopharmacol. Biol. Psychiatry |volume=29 |issue= 6 |pages= 1021-8 |year= 2005 |pmid= 15953671 |doi= 10.1016/j.pnpbp.2005.03.019 }}
*{{cite journal  | author=Millan MJ |title=Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies. |journal=Therapie |volume=60 |issue= 5 |pages= 441-60 |year= 2006 |pmid= 16433010 |doi=  }}
*{{cite journal  | author=Milatovich A, Hsieh CL, Bonaminio G, ''et al.'' |title=Serotonin receptor 1c gene assigned to X chromosome in human (band q24) and mouse (bands D-F4). |journal=Hum. Mol. Genet. |volume=1 |issue= 9 |pages= 681-4 |year= 1993 |pmid= 1302605 |doi=  }}
*{{cite journal  | author=Saltzman AG, Morse B, Whitman MM, ''et al.'' |title=Cloning of the human serotonin 5-HT2 and 5-HT1C receptor subtypes. |journal=Biochem. Biophys. Res. Commun. |volume=181 |issue= 3 |pages= 1469-78 |year= 1992 |pmid= 1722404 |doi=  }}
*{{cite journal  | author=Lappalainen J, Zhang L, Dean M, ''et al.'' |title=Identification, expression, and pharmacology of a Cys23-Ser23 substitution in the human 5-HT2c receptor gene (HTR2C). |journal=Genomics |volume=27 |issue= 2 |pages= 274-9 |year= 1995 |pmid= 7557992 |doi= 10.1006/geno.1995.1042 }}
*{{cite journal  | author=Tecott LH, Sun LM, Akana SF, ''et al.'' |title=Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. |journal=Nature |volume=374 |issue= 6522 |pages= 542-6 |year= 1995 |pmid= 7700379 |doi= 10.1038/374542a0 }}
*{{cite journal  | author=Stam NJ, Vanderheyden P, van Alebeek C, ''et al.'' |title=Genomic organisation and functional expression of the gene encoding the human serotonin 5-HT2C receptor. |journal=Eur. J. Pharmacol. |volume=269 |issue= 3 |pages= 339-48 |year= 1995 |pmid= 7895773 |doi=  }}
*{{cite journal  | author=Xie E, Zhu L, Zhao L, Chang LS |title=The human serotonin 5-HT2C receptor: complete cDNA, genomic structure, and alternatively spliced variant. |journal=Genomics |volume=35 |issue= 3 |pages= 551-61 |year= 1996 |pmid= 8812491 |doi= 10.1006/geno.1996.0397 }}
*{{cite journal  | author=Burns CM, Chu H, Rueter SM, ''et al.'' |title=Regulation of serotonin-2C receptor G-protein coupling by RNA editing. |journal=Nature |volume=387 |issue= 6630 |pages= 303-8 |year= 1997 |pmid= 9153397 |doi= 10.1038/387303a0 }}
*{{cite journal  | author=Brennan TJ, Seeley WW, Kilgard M, ''et al.'' |title=Sound-induced seizures in serotonin 5-HT2c receptor mutant mice. |journal=Nat. Genet. |volume=16 |issue= 4 |pages= 387-90 |year= 1997 |pmid= 9241279 |doi= 10.1038/ng0897-387 }}
*{{cite journal  | author=Ullmer C, Schmuck K, Figge A, Lübbert H |title=Cloning and characterization of MUPP1, a novel PDZ domain protein. |journal=FEBS Lett. |volume=424 |issue= 1-2 |pages= 63-8 |year= 1998 |pmid= 9537516 |doi=  }}
*{{cite journal  | author=Samochowiec J, Smolka M, Winterer G, ''et al.'' |title=Association analysis between a Cys23Ser substitution polymorphism of the human 5-HT2c receptor gene and neuronal hyperexcitability. |journal=Am. J. Med. Genet. |volume=88 |issue= 2 |pages= 126-30 |year= 1999 |pmid= 10206230 |doi=  }}
*{{cite journal  | author=Cargill M, Altshuler D, Ireland J, ''et al.'' |title=Characterization of single-nucleotide polymorphisms in coding regions of human genes. |journal=Nat. Genet. |volume=22 |issue= 3 |pages= 231-8 |year= 1999 |pmid= 10391209 |doi= 10.1038/10290 }}
*{{cite journal  | author=Marshall SE, Bird TG, Hart K, Welsh KI |title=Unified approach to the analysis of genetic variation in serotonergic pathways. |journal=Am. J. Med. Genet. |volume=88 |issue= 6 |pages= 621-7 |year= 2000 |pmid= 10581480 |doi=  }}
*{{cite journal  | author=Backstrom JR, Price RD, Reasoner DT, Sanders-Bush E |title=Deletion of the serotonin 5-HT2C receptor PDZ recognition motif prevents receptor phosphorylation and delays resensitization of receptor responses. |journal=J. Biol. Chem. |volume=275 |issue= 31 |pages= 23620-6 |year= 2000 |pmid= 10816555 |doi= 10.1074/jbc.M000922200 }}
}}
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{{NLM content}}
{{membrane-protein-stub}}

{{G protein-coupled receptors}}
{{Cell signaling}}

[[Category:G protein coupled receptors]]